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The Contribution of Smoking and Exposure to Tobacco Smoke to Streptococcus pneumoniae and Haemophilus influenzae Carriage in Children and Their Mothers

  1. David Greenberg1,
  2. Noga Givon-Lavi1,
  3. Arnon Broides3,
  4. Irena Blancovich4,
  5. Nechama Peled2, and
  6. Ron Dagan1
  1. 1Pediatric Infectious Disease Unit, Beer-Sheva
  2. 2Clinical Microbiology Laboratory, Soroka University Medical Center, The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva
  3. 3Primary Health Care Clinic Center, Dimona A
  4. 4Primary Health Care Clinic Center, Ksefa, Israel
  1. Reprints or correspondence: Dr. David Greenberg, Pediatric Infectious Disease Unit, Ben-Gurion University of the Negev, Soroka University Medical Center, Beer-Sheva, Israel (dudi{at}bgu.ac.il).
 
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Abstract

Background. Exposure to tobacco smoke is associated with higher risk of Streptococcus pneumoniae and Haemophilus influenzae infection. The aim of this study was to determine the influence of smoking and exposure to tobacco smoke on S. pneumoniae and H. influenzae carriage rates in children and their mothers.

Patients and methods. We performed a cross-sectional surveillance study of nasopharyngeal and oropharyngeal carriage of S. pneumoniae and H. influenzae in 208 children aged <60 months and their mothers. Smoking exposure and medical history were recorded. Carriage rates for children and their mothers in nasopharyngeal and oropharyngeal specimens were analyzed on the basis of smoking exposure.

Results. The S. pneumoniae carriage rate was higher among children exposed to smoking than among nonexposed children (76% vs. 60%; P = .016). Exposed children more frequently carried S. pneumoniae serotypes included in the conjugate 7-valent vaccine, compared with nonexposed children (49% vs. 30% of all S. pneumoniae–positive nasopharyngeal cultures; P = .02). Carriage rates of S. pneumoniae were higher among mothers who smoked than among mothers exposed to smoking and among nonexposed mothers (32%, 15%, and 12%, respectively; P = .03). There were no differences in H. influenzae carriage rates between children and mothers from smoking and nonsmoking families.

Conclusions. Exposure to tobacco smoke increased S. pneumoniae carriage rates in general and for carriage of serotypes included in the conjugate 7-valent vaccine in particular in children. Smoking mothers had a higher S. pneumoniae carriage rate than did nonsmoking mothers. Smoking or exposure to smoking did not increase H. influenzae carriage rates in children and mothers.

Cigarette smoking and exposure to environmental tobacco smoke increase the risk both of certain respiratory tract infections and of invasive diseases in adults [1, 2]. In children, exposure to smoking is associated with upper and lower respiratory tract infections, such as acute otitis media, pneumonia, and bronchitis [3–5]. Both smoking and exposure to tobacco smoke in the household are associated with carriage of bacteria, such as Neisseria meningitidis [6]. In children, the intensity of exposure to environmental smoking correlates with respiratory infection rates, especially if the mother smokes in the same room as the child [7, 8].

In young children, Streptococcus pneumoniae and Haemophilus influenzae are the most common bacterial pathogens to cause respiratory infections, such as acute otitis media and pneumonia, as well as invasive infections, such as bacteremia and meningitis [9]. In addition, Pereiro et al. [10] reported that children exposed to tobacco smoke had an increased risk for invasive H. influenzae type b disease, demonstrating a dose-dependent phenomenon.

In older individuals, these organisms are common pathogens in cases of pneumonia, bronchitis, and sinusitis; S. pneumoniae causes invasive infections in adults as well [11]. H. influenzae and S. pneumoniae can be recovered from sputum samples obtained from adult patients with chronic bronchitis [12–15]

Both organisms commonly colonize the mucosal membrane of the nasopharynx (NP) and oropharynx (OP) of healthy children, and most children are colonized with these organisms at least once during the first 2 years of life [16, 17]. The NP and OP are considered to be ports of entry to both adjacent mucosal tissues and the bloodstream for both H. influenzae and S. pneumoniae [11].

The extent of nasopharyngeal colonization versus oropharyngeal colonization with S. pneumoniae and H. influenzae differs by age. In infants and young children, S. pneumoniae colonizes mainly the NP, whereas H. influenzae colonizes the NP and OP with almost equal frequency [16, 18]. In adults, H. influenzae colonizes mainly the OP [9, 11, 18, 19], whereas S. pneumoniae can be found almost equally in the NP and OP [18, 20], and S. pneumoniae is more frequently found in the mucosal epithelium of the upper respiratory tract than elsewhere [21]. Colonization of organisms is the first step toward development of respiratory diseases, such as acute otitis media and pneumonia, as well as invasive diseases, such as bacteremia and meningitis, associated with spread of these bacteria [22]. Therefore, recognition of the risk factors for colonization is important. However, data are sparse with regard to the influence of smoking on rates of NP and OP colonization with these organisms in children and adults.

The objectives of the present study were as follows: (1) to determine the influence of smoking and exposure to tobacco smoke on S. pneumoniae and H. influenzae carriage rates in children and their mothers, (2) to determine whether exposure to smoking alters the relative proportion of NP and OP colonization with S. pneumoniae and H. influenzae, and (3) to determine whether certain S. pneumoniae serotypes were carried more frequently than other serotypes in children exposed to environmental tobacco smoke.

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Materials and Methods

The study was conducted from 1 November 2001 through 30 August 2002 at 2 primary health care clinics in 2 Jewish and Bedouin towns in southern Israel. Additional samples were obtained from the Pediatric Emergency Room of the Soroka University Medical Center (Beer-Sheva, Israel). The study was approved by the Soroka University Medical Center Ethics Committee. During the study period, no pneumococcal conjugated vaccine was licensed in Israel; thus, none of the participants were vaccinated.

Study population. Children aged 1–59 months and their mothers were enrolled. Children were brought to the primary care clinics or to the pediatric emergency department at the Soroka University Medical Center either because of acute illness or for regular examination by the primary pediatrician. An informed consent statement was signed by all mothers. Children or mothers with severe respiratory problems (such as an acute asthma attack), chronic illness (e.g., malignancies), bleeding disturbances, or anatomical abnormalities of the mouth or nose (e.g., cleft palate) were excluded from the study. In addition, all children receiving antibiotic treatment during the 3 days before enrollment were also excluded. Samples were obtained from only 1 child per family, and each child's mother was also enrolled. All mothers were healthy at enrollment, and no subjects had chronic lung disease diagnosed.

Data collection. A structured interview was conducted to document the subject's demographic characteristics (e.g., age, sex, and ethnic origin), health status, day care center attendance, antibiotic use in the month before enrollment, number of siblings, breast-feeding (of the child), concurrent illness (defined as temperature of >38°C, acute otitis media, and/or respiratory illness), smoking exposure, and medical history. Only exposure to parental smoking was recorded, because parents were considered to be the closest individuals caring for the child. Smokers other than the parents (e.g., grandmothers, grandfathers, or siblings) were noted for 18 families. However, the only smoker in the family was not a parent for only 7 children. We could not evaluate the level of exposure to these family members and decided to exclude these 7 cases. Exposure to smoke other than tobacco smoke was not recorded.

Sampling. Two samples from each individual (mother and child) were obtained: a nasopharyngeal sample was obtained by use of a flexible swab stick with Dacron or Rayon tip that was inserted into the nostril until resistance was found, and oropharyngeal samples were obtained by direct inspection of the posterior wall and tonsillar regions using rigid cotton-tipped applicators. The swabs were inoculated into modified Stewart transport medium (Transwab MW173 Transport Medium; Medical Wire and Equipment) and were brought to the Clinical Microbiology Laboratory of the Soroka University Medical Center within 16 h.

Bacteriology. For the detection of S. pneumoniae, swabs were inoculated onto Colombia agar with 5% sheep blood and gentamicin, 5.0 µg/mL, and were incubated aerobically at 35°C for 48 h. S. pneumoniae was identified by colony morphology, α-hemolysis, and inhibition by optochin and was confirmed by a positive result of a slide agglutination test (Phadebact; Pharmacia Diagnostics). Pneumococcal serogrouping and serotyping were performed on 1 colony sample on the basis of capsular swelling (quellung reaction) using antisera provided by the Statens Seruminstitut (Copenhagen, Denmark). The following serotypes were classified as vaccine serotypes (VT) because they are included in the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7): 4, 6B, 9V, 14, 18C, 19F, and 23F. Serotypes 6A and 19A were considered to be VT-related serotypes. Analyses of VT and VT-related serotypes were performed separately.

Identification of H. influenzae was based on Gram stain findings, growth on chocolate-agar medium, failure to grow on trypticase agar with added sheep blood, and the nutritional requirement of both hemin and nicotine adenine nucleotide. Organisms that failed to agglutinate with polyvalent antisera to H. influenzae groups a, b, and c—f (Phadebact; Pharmacia Diagnostics) were considered to be nontypeable.

Statistical analysis. Data were recorded using the Access office software (Microsoft). Statistical analysis was performed using SPSS software, version 12.0 (SPSS). Analyses were performed separately for children and mothers. Children were divided into the following 2 groups: (1) Children with nonsmoking parents (i.e., children with no exposure to tobacco smoke) and (2) children exposed to at least 1 smoking parent (i.e., children with exposure to tobacco smoke). Mothers were divided into the following 3 groups: (1) families with nonsmoking parents (i.e., mothers with no exposure to tobacco smoke), (2) families in which only the father smoked (i.e., mothers with exposure to tobacco smoke), and (3) families in which the mother smoked. Contingency table analysis for comparing rates between unmatched samples was performed using the χ2 test or Fisher's exact test, as appropriate. χ2 Analyses for linear trend in proportions were performed for carriage rates of S. pneumoniae in the 3 tobacco smoke exposure categories. Tests for significance on continuous variables were performed using Student's t test. Multivariate logistic regression models were used to examine the effects of multiple risk factors on S. pneumoniae total carriage and for serotype groups, as well as for H. influenzae carriage in children and mothers. Variables implicated in the literature or that were statistically significant at the level of P < .1 in univariate analyses were included in the multivariate logistic regression models. These potential risk factors were sex, antibiotic treatment during the month before sampling, day care attendance, age, health status (i.e., being healthy vs. being sick, with sickness defined as fever [temperature, >38°C], acute otitis media, and/or respiratory illness), mother's level of education, breast-feeding (of the child), number of siblings, place of study enrollment (community or emergency department), and ethnicity. ORs were used to measure the association between exposures status. A P value <.05 was considered to be statistically significant in multivariate analyses.

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Results

Nasopharyngeal and oropharyngeal samples were obtained from 216 mothers and their 216 offspring. All swabs were plated for both S. pneumoniae and H. influenzae. Data regarding the smoking behavior of the parents were available for 208 (96%) of 216 families. Data on smoking or exposure to tobacco smoke were available for 204 (94%) of 216 the mothers.

Ninety-three (45%) of the 208 children had nonsmoking parents, and 115 (55%) were exposed to tobacco smoke. No significant differences were found between nonexposed and exposed children with regard to the child's mean age, the child's mother's age, the child's sex, the mother's level of education, the presence of illness at the time of culture, the number of siblings, day care center attendance, and antibiotic treatment in the month before sampling (table 1).

Table 1
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Table 1

Comparison of demographic and clinical characteristics between smoking and nonsmoking families.

The S. pneumoniae carriage rate was higher among children exposed to tobacco smoke than among those who were not exposed (87 [76%] of 115 children vs. 56 [60%] of 93 children; P = .016). This difference was seen both for NP carriage (85 [74%] of 115 children vs. 55 [59%] of 93 children; P = .024) and for OP carriage (27 children [24%] vs. 12 children [13%]; P = .052) (figure 1).

Figure 1
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Figure 1

Nasopharyngeal (NP) and oropharyngeal (OP) carriage rates of Streptococcus pneumoniae in children with nonsmoking parents, compared with rates in children with 1 or 2 smoking parents (i.e., passive smoking children).

Children exposed to tobacco smoke had not only significantly higher isolation rates for S. pneumoniae than did children who were not exposed to tobacco smoke, but they had also a significant increase in carriage of PCV7 serotypes (41 [49%] of 83 children vs. 16 [30%] of 54 children; P = .022) (figure 2). Analysis of OP carriage of PCV7 serotypes showed the same trend (12 [10%] of 115 children exposed to tobacco smoke vs. 4 [4%] of 93 children who were not exposed to tobacco smoke; P = .099). These differences still remained after adjustment for sex, antibiotic treatment in the month before sampling, day care attendance, age, health versus illness, mother's level of education, breast-feeding (of the child), number of siblings, site of enrollment (community or emergency room), and ethnicity by multivariate logistic regression analysis. For children who did not attend a day care center, the carriage rate of PCV7 serotypes was significantly higher for children who were exposed to smoking than for children who were not exposed to tobacco smoke (23 [38%] of 60 children vs. 9 [16%] of 57 children; P = .006). This difference was not statistically significant for children who attended a day care center.

Figure 2
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Figure 2

Distribution of Streptococcus pneumoniae serotypes in children with positive nasopharyngeal culture results for children with nonsmoking parents and those exposed to tobacco smoke. VR, vaccine-related serotypes (i.e., serotypes 6A and 19A); VT, vaccine serotype.

Carriage rates of S. pneumoniae in mothers increased linearly, from 11 (12%) of 93 mothers who were not exposed to tobacco smoke, to 13 (15%) of 86 mothers who were exposed to tobacco smoke, and to 8 (32%) of 25 smoking mothers (P = .031). This linear trend was mainly associated with NP carriage of S. pneumoniae (5 [5%] of 93, 9 [10%] of 86, and 5 [20%] of 25 mothers, respectively; P = .026) (figure 3).

Figure 3
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Figure 3

Carriage of Streptococcus pneumoniae in mothers, by smoke exposure. The line labeled “A” is the estimation line for total S. pneumoniae carriage (P = .031, by χ2 analysis for linear trend in proportions). The line labeled “B” is the estimation line for nasopharyngeal S. pneumoniae carriage, with or without oropharyngeal (OP) carriage (P = .026, by χ2 analysis for linear trend in proportions). NP, nasopharyngeal.

All H. influenzae isolates were non—type b. No significant differences in H. influenzae total carriage rates were found between children with nonsmoking parents and children with at least 1 smoking parent (63 [68%] of 93 children vs. 86 [75%] of 115 children; P = .263). Analysis of all positive culture results revealed no significant differences between children with nonsmoking parents and those with at least 1 smoking parent by site of isolation (for NP alone, 21 [33%] of 63 children vs. 28 [33%] of 86 children; for OP alone, 17 children [27%] vs. 18 children [21%]; and for both NP and OP, 25 children [40%] vs. 40 children [47%]).

The total carriage rate for H. influenzae in mothers was similar in the 3 groups (32 [34%] of 93 mothers who were not exposed to tobacco smoke, 36 [42%] of 86 mothers who were exposed to tobacco smoke, and 9 [36%] of 25 actively smoking mothers). Analysis of all positive culture results revealed no significant differences by site of isolation (NP alone, OP alone, or both NP + OP) among mothers not exposed to tobacco smoke (for NP site alone, 3 [9%] of 32, 3 [8%] of 36, and 1 [11%] of 9 tobacco-nonexposed mothers, tobacco-exposed mothers, and smoking mothers, respectively; for OP site alone, 26 [81%] of 32, 29 [81%] of 36, and 7 [78%] of 9 tobacco-nonexposed mothers, tobacco-exposed mothers, and smoking mothers, respectively; and for both NP and OP sites, 3 [9%] of 32, 4 [11%] of 36, and 1 [11%] of 9 tobacco-nonexposed mothers, tobacco-exposed mothers, and smoking mothers, respectively).

In multiple logistic regression models controlling for sex, antibiotic treatment in the month before sampling, day care attendance, age, health versus illness, mother's level of education, breast-feeding, number of siblings, site of enrollment (community or emergency room), and ethnicity, the increased rates of S. pneumoniae carriage among smoking mothers remained independently significant, whereas rates of H. influenzae rates were not significant.

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Discussion

In the present study, we demonstrated that children exposed to smoking parents had a significantly higher rate of S. pneumoniae carriage than did children who were not exposed to tobacco smoke. The increased carriage rate in individuals exposed to tobacco smoke was seen both in NP and OP specimens. The increased OP colonization may be a predisposing factor to additional spread, resulting in lower respiratory tract infections. This could be further increased during coinfection with respiratory viruses, such as influenza viruses in children [23]. Our findings might explain previous reports demonstrating that children exposed to environmental tobacco smoke more frequently experience respiratory infections, such as acute otitis media and pneumonia [7, 24].

Smoking and passive exposure to tobacco smoke is associated with the carriage of potentially pathogenic bacteria, possibly as a result of enhanced bacterial binding to the respiratory epithelial cells of smokers [25]. Moreover, in a study that investigated the carriage rates of anaerobic bacteria in smokers versus nonsmokers, it was found that nonsmokers carried more anaerobic bacteria. This study also demonstrated that these anaerobic bacteria interfered with pathogenic bacteria, such as S. pneumoniae and H. influenzae, in the nasopharynx. Thus, exposure to smoke reduces the number of anaerobic bacteria in the nasopharynx and probably enhances the potential of pathogenic bacteria [26]. In our study, VT serotypes of S. pneumoniae were carried more frequently by children exposed to a smoking parent. These serotypes cause more respiratory and invasive S. pneumoniae diseases than do non-VT serotypes [27, 28]. A plausible speculation is that the VT serotypes are better fit to colonize the respiratory epithelium, in general, and the damaged and inflamed epithelium, in particular.

In the present study, we found that, for children who were not attending day care centers, the carriage rate of PCV7 serotypes was significantly higher among children exposed to smoking than among those who were not exposed to smoking. These differences were not found in children who were attending day care centers. This may be explained by longer exposure to a smoking parent when the child remains at home. Our findings suggest that the potential protection against respiratory infections given to children by staying at home rather than attending a day care center may be hampered by increased exposure to smoking.

Smoking mothers had a higher S. pneumoniae carriage rate than did mothers exposed to tobacco smoke, mainly because of increased NP colonization rates. In adult patients with chronic obstructive pulmonary disease, colonization with S. pneumoniae is common [29]. This colonization occurs mainly in the lower respiratory tract, and the organism can be isolated from sputum samples obtained from these patients. New colonization with S. pneumoniae often precedes exacerbation of chronic bronchitis in adults [14]. Our findings suggest that, in adults (as in children), the spread of colonization from mainly one site (OP) to an additional site (NP) is the first step toward additional spread, which may result in either lower or upper respiratory tract infection. Furthermore, smoking and exposure to tobacco smoke was shown to increase the risk of invasive S. pneumoniae infection [2].

One of the limitations of the present study is the fact that tobacco exposure was measured on the basis of questionnaires. The parents' reporting might be inaccurate and, thus, children exposed to heavy smokers might be included with children who were exposed less intensively to environmental tobacco smoke. In this study, cotinine levels were not measured. Previous studies measured cotinine levels in urine samples to determine the amount of tobacco exposure in children [5]. However, in one study, which used a questionnaire to compare urine cotinine levels and parental history as indicators of exposure to tobacco smoke, the authors concluded that urinary cotinine level did not necessarily improve the assessment of exposure to smoking and its relation to lower respiratory illness in infants [30]. Another limitation of the present study is that it was a point prevalence study, and use of a single culture can underestimate the rate of colonization. However, the chance of missing colonization was equal for all children, and thus probably did not affect the findings when exposed and nonexposed children were compared.

In summary, we found that, in both children and mothers, exposure to tobacco smoke increased S. pneumoniae carriage rates. In children, this increased carriage rate was mainly seen for VT serotypes. In contrast to S. pneumoniae, rates of H. influenzae carriage were not higher in children or mothers exposed to tobacco smoke. It is suggested that increased colonization of S. pneumoniae in persons exposed to tobacco smoke is the first step leading to an increase in respiratory tract infections or invasive infections caused by S. pneumoniae.

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Acknowledgments

Potential conflicts of interest. All authors: no conflicts.

  • Received July 14, 2005.
  • Accepted November 29, 2005.
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  1. Clin Infect Dis. (2006) 42 (7): 897-903. doi: 10.1086/500935
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